NAFLD and NASH – SC410

Non-Alcoholic Fatty Liver Disease | SC410

Non-alcoholic fatty liver disease (NAFLD) is a common condition associated with the buildup of excess fatty acid triglycerides in liver cells not caused by alcohol use. It occurs in patients who drink little or no alcohol, and is one of the most common cause of chronic liver disease in the United States. Most patients are asymptomatic and do not experience any complications from the disease. However, the fat that accumulates in some patients with NAFLD can cause inflammation and scarring in the liver. This more serious form of NAFLD is called non-alcoholic steatohepatitis (NASH). NASH is liver inflammation caused by a buildup of fat in the liver, which causes decreased liver function and can lead to cirrhosis, liver failure and end-stage liver disease. While NASH is most common in insulin-resistant obese adults with diabetes and abnormal serum lipid profiles, its prevalence is increasing among juveniles as obesity rates increase within this patient population. It can slowly progress to a loss of hepatic function, irreversible liver damage and ultimately cirrhosis and hepatocellular carcinoma. NASH is the third-leading and fastest growing cause of liver transplantation in the United States, accounting for approximately 7.4% of liver transplants in 2010.

How NAFLD Progresses

Studies have shown that metabolic abnormalities, such as diabetes, hypertension, dyslipidemia and obesity, are associated with a significant increase in the number of NAFLD patients progressing to NASH and advanced fibrosis. NAFLD is the most common liver disorder among adults in the Western world. Normally the liver contains some fat, but if more than 5-10% of the liver’s weight is fat, then it is referred to as fatty liver, or steatosis. The spectrum of NAFLD ranges from simple steatosis to NASH, which can ultimately progress to end-stage liver disease. In addition to the accumulation of fat in the liver, NASH is characterized by inflammation and cellular damage with or without fibrosis. NASH can lead to fibrosis and eventually progress to cirrhosis, portal hypertension, esophageal varices, ascites, or liver failure. Progression to cirrhosis and other late stage complications can occur within 5 to 10 years after initial NASH diagnosis. NASH patients with obesity or type-2 diabetes are at a significantly higher risk of disease progression. Once the disease advances beyond NASH to these life-threatening conditions, liver transplantation is the only alternative. The following image provides an overview of the progression of NAFLD from a healthy liver to cirrhosis:

NAFLD

Market Opportunity and Currently Available Treatments and Their Limitations:
Within the United States, NAFLD represents one of the most common causes of liver disease. According to the National Digestive Diseases Information Clearinghouse, between 30 and 40 percent of adults in the US have NAFLD, of which about 3 to 12 percent (10 million to 40 million) suffer from NASH. NASH is becoming more common, largely secondary to the obesity epidemic that faces the nation as well as associated metabolic syndrome and type-2 diabetes. From 1980 to 2010, the rate of obesity in the United States alone has more than doubled in adults, more than tripled in children, and is expected to increase by an additional 33% over the next two decades. Globally, the rate of obesity has also nearly doubled since 1980 and is expected to double again by 2030 if nothing is done to reverse the epidemic. NASH is one of the main causes of liver cirrhosis, behind hepatitis C and alcoholic liver disease, and is the fastest growing cause of liver transplantation in the United States. Currently, NASH and NAFLD are under-diagnosed due to poor disease awareness, the insufficiency of non-invasive diagnostic tools and the lack of effective approved therapies. NAFLD/NASH represent a substantial unmet medical need.

According to GlobalData UK Ltd, the estimate for NASH market sales in 2016 is approximately $618m across seven major markets, which include the United States, France, Germany, Italy, Spain, UK, and Japan. Furthermore, the NASH market is forecasted to grow over a 10-year period at a compound annual growth rate (CAGR) of 45.0% across the seven major markets. It is projected that the United States will account for around 88% of global sales, and that the global market for NASH will balloon to $25.3 Billion by the end of 2026.

SC410 Solution for NAFLD

SC410 is our proprietary product candidate that is being developed for the treatment of NAFLD. SC410 consists of a complex proprietary mixture of various fatty acids, formulated using ALT® to specifically address the treatment of NAFLD. The drug is encapsulated in a soft gelatin capsule and intended to be taken orally. We believe SC410 can substantially reduce the triglycerides in the blood and therefore, reduce the amount of fat in the liver. Recent research showed that increasing the amount of omega-3 fatty acids delivered to the membrane of the red blood cells resulted in a reduction of fat in the liver.

We recently conducted a nine-week animal trial of SC410. In the trial, the group of animals that received the ALT formulated material demonstrated a reduction in overall body weight as compared to the control group that received placebo. In addition, the liver weight of the animals in the active group was less than that of those in the placebo and most importantly, the liver tissue itself had statistically significant less (p < 0.05) triglycerides. These results indicate that SC410 may be a promising treatment candidate for NAFLD.

The WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with Omacor Therapy) study evaluated the effects of purified eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in NAFLD. In a randomized, placebo-controlled trial, the WELCOME Study tested the hypothesis that 15-18 months treatment with the highest licensed dose (4g/day) of DHA+EPA was effective in ameliorating the early stages of NAFLD, with primary outcomes related to: a) liver fat measured by magnetic resonance spectroscopy scan in three discrete liver zones, and b) two algorithmically derived, histologically validated, liver fibrosis scores. The study monitored adherence to the intervention in the DHA+EPA group, and potential contamination in the placebo group, by measuring erythrocyte enrichment of DHA or EPA between baseline and end of the study. We believe that the results from this study provides support for our belief that combining a unique ratio of omega-3 fatty acids, formulated using ALT, will result in a higher amount of polyunsaturated fatty acids delivered and incorporated into the cell membrane and therefore, may reduce the excess fat build up in the liver and improve the absorption lost as a result of NAFLD and hopefully, slow the disease’s progression to NASH.